Extracellular matrix dynamics during mesenchymal stem cells differentiation

Abstract

Mesenchymal stem cells (MSCs) are stromal cells that display self-renewal and multipotent differentiation capacity. The repertoire of mature cells generated ranges but is not restricted to: fat, bone and cartilage. Their potential importance for both cell therapy and maintenance of in vivo homeostasis is indisputable. Nonetheless, both their in vivo identity and use in cell therapy remain elusive. A drawback generated by this fact is that little is known about the MSC niche and how it impacts differentiation and homeostasis maintenance. Hence, the roles played by the extracellular matrix (ECM) and its main regulators namely: the Matrix Metalloproteinases (MMPs) and their counteracting inhibitors (TIMPs and RECK) upon stem cells differentiation are only now beginning to be unveiled. Here, we will focus on mesenchymal stem cells and review the main mechanisms involved in adipo, chondro and osteogenesis, discussing how the extracellular matrix can impact not only lineage commitment, but, also, their survival and potentiality. This review critically analyzes recent work in the field in an effort towards a better understanding of the roles of Matrix Metalloproteinases and their inhibitors in the above-cited events.

<p>Functionalized Graphene Nanoparticles Induce Human Mesenchymal Stem Cells to Express Distinct Extracellular Matrix Proteins Mediating Osteogenesis</p>

“…When exogenous MSCs interact with biomimetic scaffolds, they can trigger the endogenous cells to produce ECM, or the MSCs themselves can express ECM proteins to form the matrix. [6][7][8][9] Thus, understanding the niche signals that are triggered, for instance, evaluating the ECM that is generated when MSCs are seeded onto a scaffold and implanted in a bone defect will help the consistency and efficacy of bone tissue engineering and regenerative medicine approaches. 10 During osteogenic differentiation, cells initiate the synthesis of ECM, and express osteocyte-specific markers such as alkaline phosphatase, osteopontin and osteocalcin, thus enabling the cell to progress through bone cell development.…”

Adhesion and differentiation behaviors of mesenchymal stem cells on titanium with micrometer and nanometer‐scale grid patterns produced by femtosecond laser irradiation

“…Human mesenchymal stem cells (hMSCs) are appropriate candidate cells to study the potential effects of Ti surfaces with designed topographies as they are present in many different tissues and are thought to be one of the first cells involved in the repair of orthopedic injuries . hMSCs can also differentiate into a variety of different lineages when cultured in differentiation induction medium or on various substrates in vitro …”

“…[14][15][16][17] hMSCs can also differentiate into a variety of different lineages when cultured in differentiation induction medium or on various substrates in vitro. 11,[18][19][20] We examined the effect of surface topography on hMSC adhesion and differentiation in the present study by producing Ti surfaces with micrometer-and nanometer-scale grids using femtosecond laser irradiation and evaluating the subsequent adhesion and differentiation of hMSCs.…”

The role of extracellular matrix stiffness in regulating cytoskeletal remodeling via vinculin in synthetic smooth muscle cells

“…ECM stiffness regulates cell migrations, affects directly cancer metastasis,[11, 12] and plays an essential role in stem cell differentiation. [13] However, few studies have focused on how ECM stiffness alters VSM cell behaviors. [8] Among possible cell mechanotransduction pathways—ion channels, actin cytoskeleton adaption, and G-protein-coupled receptors (GPCR)[14, 15]—cell cytoskeleton remodeling through focal adhesions (FAs) has been considered to be a more important mechanism.…”